The HIV virus responsible for causing AIDS enters immune cells through a multi-step process (Berger, AIDS 11:S3-16 (1997); Doranz, et al, Immunol. Res. 16:15-28 (1997)). Initially, gp120 located on the HIV viral surface binds to a CD4 receptor on the surface of the host cell. This causes the gp120 protein to undergo a conformational change that allows it to bind to a second cell surface receptor, CCR5 (Dragic, et al., Nature 381:667-673 (1996); Deng, et al., Nature 381:661-666 (1996)). It is this second binding step that ultimately leads to membrane fusion and viral entry.
Biochemical studies have revealed that a portion of the CCR5 receptor near its amino terminus is critical for interaction with gp120 and that there are several sulfated tyrosines in this region that are essential for binding (Farzan, et al, J. Virol. 72:1160-1164 (1998); Farzan, et al., Cell 96:667-676 (1999)). Attempts have been made to model peptides based upon the CCR5 binding region and use them to block the entry of HIV into immune cells (Farzan, et al., J. Biol. Chem. 275:33516-33521 (2000); Cormier, et al., Proc. Nat'l Acad. Sci. 97:5762-5767 (2000)). However, the peptides that have been developed thus far appear to have relatively low affinity for gp120 and this may ultimately limit their clinical usefulness.
In an alternative approach, researchers have attempted to make antibodies against gp120 that block the entry of HIV into host cells (see, e.g., Cole, et al., Virology 290:59-73 (2001); Fouts, et al., J. Virol. 71:2779-2785(1997); Ho, et al., J. Virol. 65:489-493 (1991)). Although antibodies of this type have a high affinity for antigen, developing them for use as a long term therapy may be difficult and the cost of production is likely to be quite expensive.